Improved means for the synthesis of organic molecules, particularly of complex molecules such as those common to biological and medicinal systems, constitutes an important part of research today. Known synthesis routes often result in only minor yields of important products and/or are totally foreclosed by the presence of interfering reactive sites present on available precursors for the products.
One important and common step in such synthesis involves the joinder of desired molecules through a carboxylic linkage unit such as an ester, amido or amide group. Representative of the molecularly complex products of this step are such important and varied compounds as:
Glycocholic acid--a clinical stimulent for bile secretion;
Taurocholic acid--a useful intermediate, the sodium salt of which is a lipase accelerator;
Ethyl cholandienate--described in U.S. Pat. No. 2,725,388;
Basic esters of bile acids--described in U.S. Pat. No. 2,562,350; and
Nucleoside esters of steroids--described in U.S. Pat. No. 4,418,059 of this inventor.
Many of these compounds cannot practically be produced by conventional techniques such as use of acyl chloride intermediates or the like. Where there exists an active site--including oxygens such as alcohol and ketone groups or an amino group--interference, instability and/or other problems arise.
There exist many other known synthesis routes for the formation of these carboxylic linkage units. One of these routes involves use of a mixed anhydride intermediate. This route is described and exemplified in the literature including the Journal of the American Chemical Society at 80, 5714; 74, 3309; 73, 118; and 72, 5530; Organic Synthesis at 37, 20; Journal of Organic Chemistry at 28, 1905 and elsewhere. The prior art, however, reflects no appreciation that these mixed anhydrides may be utilized to overcome the foregoing problems of synthesis and to facilitate the production of many important end-products.